MCID: 3MT013
MIFTS: 33

3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Ear diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards integrated aliases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

Name: 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 54 12 24 25 71 29 13 14 69
Megdel Syndrome 12 23 50 25 56
Serac1 Defect 23 50 25
Megdel 12 24 71
Megdhel Syndrome 23 25
Mgca6 12 71
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy, and Leigh-Like Syndrome 25
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy and Leigh-Like Syndrome 69
3-Methylglutaconic Aciduria with Deafness, Encephalopathy,leigh-Like Syndrome 23
3-Methylglutaconic Aciduria with Deafness-Encephalopathy-Leigh-Like Syndrome 56
3-Methylglutaconic Aciduria, Type Vi 71
3-Methylglutaconic Aciduria Type Vi 50
3-Methylglutaconic Aciduria Type 6 12

Characteristics:

Orphanet epidemiological data:

56
megdel syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood


HPO:

32
3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

OMIM : 54
MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (256000). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by Wortmann et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (614739)

MalaCards based summary : 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome, also known as megdel syndrome, is related to 3-methylglutaconic aciduria and leigh-like syndrome, and has symptoms including failure to thrive, dystonia and recurrent infections. An important gene associated with 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome is SERAC1 (Serine Active Site Containing 1). Affiliated tissues include brain.

UniProtKB/Swiss-Prot : 71 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome: An autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells.

Genetics Home Reference : 25 MEGDEL syndrome is an inherited disorder that affects multiple body systems. It is named for several of its features: 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E), and Leigh-like disease (L).

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the SERAC1 gene on chromosome 6q25.

GeneReviews: NBK195853

Related Diseases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:



Diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Abdomen- Gastroin testinal:
feeding problems

Immunology:
recurrent infections
neonatal sepsis

Metabolic Features:
lactic acidosis
hypoglycemia

Head And Neck- Head:
microcephaly (1 patient)

Muscle Soft Tissue:
hypotonia
degrading mitochondria

Neurologic- Central Nervous System:
mental retardation
dystonia
spasticity
psychomotor retardation
cerebellar atrophy
more
Head And Neck- Ears:
hearing loss, sensorineural

Laboratory- Abnormalities:
increased serum lactate
hyperammonemia
3-methylglutaconic aciduria
defects in mitochondrial oxidative phosphorylation
abnormal phospholipid profile
more

Clinical features from OMIM:

614739

Human phenotypes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

32 (show all 23)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 dystonia 32 HP:0001332
3 recurrent infections 32 HP:0002719
4 spasticity 32 HP:0001257
5 seizures 32 occasional (7.5%) HP:0001250
6 encephalopathy 32 HP:0001298
7 global developmental delay 32 HP:0001263
8 lactic acidosis 32 HP:0003128
9 increased serum lactate 32 HP:0002151
10 hyperammonemia 32 HP:0001987
11 intellectual disability 32 HP:0001249
12 hypoglycemia 32 HP:0001943
13 cerebellar atrophy 32 HP:0001272
14 brain atrophy 32 HP:0012444
15 feeding difficulties 32 HP:0011968
16 muscular hypotonia 32 HP:0001252
17 3-methylglutaconic aciduria 32 HP:0003535
18 developmental regression 32 HP:0002376
19 sensorineural hearing impairment 32 HP:0000407
20 neonatal sepsis 32 HP:0040187
21 abnormality of extrapyramidal motor function 32 HP:0002071
22 abnormality of the coagulation cascade 32 HP:0003256
23 aplasia/hypoplasia involving the central nervous system 32 HP:0002977

UMLS symptoms related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:


muscle spasticity, abnormality of extrapyramidal motor function

Drugs & Therapeutics for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Genetic Tests for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Genetic tests related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

id Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 29 24 SERAC1

Anatomical Context for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

39
Brain

Publications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

71
id Symbol AA change Variation ID SNP ID
1 SERAC1 p.Gly401Asp VAR_068442
2 SERAC1 p.Gly404Glu VAR_068443
3 SERAC1 p.Ser498Thr VAR_068445 rs201941476

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh37 Chromosome 6, 158567859: 158567859
2 SERAC1 SERAC1, IVS13DS, G-C, +1 single nucleotide variant Pathogenic
3 SERAC1 SERAC1, 4-BP DEL, 1167TCAG deletion Pathogenic
4 SERAC1 SERAC1, 3-BP DEL, 1435CTT deletion Pathogenic
5 SERAC1 SERAC1, 2-BP DUP, 1627TC duplication Pathogenic
6 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh37 Chromosome 6, 158571548: 158571548
7 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh37 Chromosome 6, 158571484: 158571485
8 SERAC1 NM_032861.3(SERAC1): c.1643_1646dup (p.Leu550Serfs) duplication Pathogenic rs761964407 GRCh37 Chromosome 6, 158535859: 158535862
9 SERAC1 NM_032861.3(SERAC1): c.1403+1G> C single nucleotide variant Pathogenic rs1131690799 GRCh38 Chromosome 6, 158117726: 158117726

Expression for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome.

Pathways for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

GO Terms for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Cellular components related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.02 AUH DNAJC19 OPA3 SERAC1 TMEM70

Biological processes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 8.62 DNAJC19 OPA3

Sources for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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